In honour of AMD Awareness Month, Dr. Michael Tolentino of the Center for Retina & Macular Disease in Florida was kind enough to write a guest post for AMDblog.org. In this article, Dr. Tolentino discusses the progression of AMD, treatment methods and more.
Just a decade ago, if you we were given the diagnosis of macular degeneration, these words would strike fear in both patients and physicians. But because of advances in research, funded by such organizations as Foundation Fighting Blindness, we are close to eliminating blindness from this condition.
The way we have been able to develop treatments for this condition is a direct result of our understanding of the disease and the disease process. By observing patients with macular degeneration and understanding the problem, we have been able to develop not only treatments that can slow down the disease, but also treatments that can restore vision if caught in time.
There are two stages to macular degeneration and the process of developing macular degeneration is actually life long. The early stage is the asymptomatic stage. This is typically a stage that occurs before the age of 65. This stage encompasses the time when there are no signs visible in the eyeball, to the stage when there are numerous deposits called drusen visible in the macular region. I call this stage the “rusting stage” or the oxidation stage. When we are born, we start to oxidize or rust. Fortunately, our bodies have innate defenses against rusting. In the eyeball, the “factory rust protection”, is found in macular pigment. Unfortunately, like all things, the protectant breaks down over time leaving our maculas vulnerable the older we get. With the breakdown of this macular pigment, over time and as we age, rust starts to appear in the unprotected area of the macula. This rust is called drusen and it is the hallmark of dry macular degeneration.
The rust particles lead to asymptomatic and advanced macular degeneration. Over time, the rust leads to corrosion. Corrosion appears like holes in the macula, holes which we call geographic atrophy. This corrosion will slowly lead to increasing loss of vision as the holes expand and become confluent.
Unfortunately, this rust or drusen also causes new blood vessels to form that grow into or under the rust. And these new blood vessels can either leak or bleed, resulting in a blister to form in the very center of our vision. Because of the rapidity of this blister formation, wet macular degeneration is considered a very serious blinding condition. The bleeding and leaking which results in the blister forming inside the eye is what eventually leads to severe and profound visual loss. It was because of this stage of disease that made macular degeneration at one time the leading cause of blindness in the developed world.
Understanding the problem has now led to preventative therapies and restorative treatments for both dry and wet macular degeneration. To prevent the development of macular degeneration the main focus of research was to determine what the innate rust protection or antioxidant the body had when we were young which we lost as we got older. We knew the criteria that could allow us to isolate this factory rust protection . This factory rust protection would be (1) a potent anti-rust molecule (anti-oxidant), (2) It would localize in the center of the macula, called the fovea, and (3) in patients developing macular degeneration this protectant would diminish as we age, and would be difficult to replenish.
Knowing what to look for unfortunately did not make it easy to discover what this substance was. But thanks to advances in organic chemistry, we were able to identify this substance.
The true macular protectant and factory rust protectant of the macula is now known to be three molecules in the class of carotenoids. These 3 molecules, meso-zeaxathin, lutein and zeaxanthin in a distinct ratio truly make up the native factory rust protection of the eye. How do we know this?
- These three carotenoids are very potent antioxidants. What’s interesting is that combined together in a distinct ratio these carotenoids work synergistically and are more effective antioxidants than each of the molecules individually. We know that meso-zeaxanthin is the most potent antioxidant of the three. But even more potent that meso-zeaxanthin alone is combining it with lutein and zeaxanthin. This almost increases its potency as an anti-oxidant by two fold.
- These molecules focalize and situate and stay within the macula, which is the very center of the retina in the back of the eye.
- This macular pigment protectant are found in very high levels when we are younger and diminishes after the age of 45 and continues to diminish as we age.
- Another one of its properties is its ability to filter out blue light, which is the wavelength of light that accelerates macular degeneration and oxidation in the retina.
Having discovered what consists of the true macular protectant, the next step in research is to determine how we can restore these molecules into the eye. Initially, we attempted to see if dietary intake alone could accomplish this. While dietary intake of green leafy vegetables enable people to obtain two out of the three carotenoids, mesozeaxanthin which is the critical carotenoid is not obtainable by diet. Because of this inability to obtain this critical carotenoid from the diet, supplements were developed in the form of MacuHealth to restore all three carotenoids. Several studies have demonstrated that to restore the correct levels of macular protectant, all three carotenoids had to be ingested as a supplement. They also demonstrated that just replacing two out of the three was inadequate in restoring the protectant in the foveal region. This breakthrough in research has allowed us to develop a restorative strategy for the protectant of the macula. In essence, this is like vitamin D and calcium therapy to prevent osteoporosis, or wearing sunscreen when you live in Florida, or using toothpaste with fluoride. All these strategies have one thing in common: restoring what we lose as we age and preventing decay and destruction.
Using the MacuHealth formulation represents the only means of restoring the natural macular protectant and will slow down the development of macular degeneration.
Currently we have developed several effective medicines to treat patients with wet macular degeneration. These treatments were discovered in a very similar fashion as the macular pigment restoration therapy with MacuHealth. These medicines were developed by understanding the underlying problem and then searching for the molecular cause of the problem.
Wet macular degeneration is a different problem than rusting. We knew the properties of a molecule that would cause wet macular degeneration. These properties were described as far back as 1945. We realized that wet macular degeneration was caused by a molecule or set of molecules that caused blood vessels inside the eye to leak and to grow.
These molecules or molecule have the following properties:
- The factor causes leaking and bleeding by new and old blood vessels.
- This molecule was usually not found in large quantities in the eye, but is upregulated by oxidation (rust)
- It also had to be found in the disease of wet macular degeneration.
While we knew what to look for, it took almost 4 decades to discover what this molecule was. And in the 1990’s we discovered that the cause of new blood vessel growth and blister formation in wet macular degeneration was a factor called Vascular Endothelial Growth Factor (VEGF). VEGF had all the properties that we were looking for in the causative agent for wet macular degeneration. It caused blood vessels that were normal to leak profusely. (1)It promoted blood vessels to grow. Oxidative by products like rust or free radicals, which are a result of oxidation or cause oxidation, were able to upregulate VEGF. (4) We discovered that this was in fairly high quantities in diseases like wet macular degeneration.
I was fortunate to have been on the research team that discovered the culprit causing wet macular degeneration, or the blistering the molecule called vascular endothelial growth factor (VEGF). I was also on the initial research team that set out to develop molecules that could block or stop the effect of this VEGF a molecule currently called Avastin. From the concept of discovering the molecule and developing the blocker for this molecule, to the eventual development of a treatment that can be used in humans, took approximately one decade. Currently we have 4 medicines that we use to treat our patients with wet macular degeneration. These medicines include Eylea, Lucentis, Avastin and Macugen.
In my next blog, I am going over the differences between these medicines. Suffice it to say these medicines which are injected into the eyeball once a month, has been demonstrated to keep people from going blind or improving vision after the wet macular degeneration has set in and caused visual loss
In summary, understanding the disease, research, and developing therapies, has led to a world where we will likely no longer see such devastating visual loss in our patients. Of course we still need to improve on these therapies but these will serve as a base for accomplishing the goal of eradicating blindness from macular degeneration.
About the author: Dr. Michael Tolentino is a retinal specialist at the Center for Retina & Macular Disease. He has helped develop all current treatments for wet macular degeneration and has more than 80 peer reviewed publications. Dr. Tolentino is also a leader in charitable organizations including the Board Member Restoring Sight International.
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